Patent GB-825210-A (GB)
Title: Dehydro-compounds of the steroid series and process for their manufacture
IPC: C12P33/00
Filed: 1956-02-06
Abstract: The invention comprises D 1,4-pregnadiene compounds having a 9a -halo substituent and/or an 18-free or functionally converted hydroxy or oxo group, also 1,6-bisdehydro-cortexone, 1,11-bisdehydro - progesterone, 1 - dehydro - 17a  - methyl- and 1 - dehydro - 17a  - ethinyl - testosterone, 17a  - methyl - 3,20 - dioxo - 1,4 - bisdehydropregnanes, 1 - dehydro - 11 - oxo - 17a  - methyl-cortexone and their functional derivatives, together with a process for the manufacture of 1,4-bisdehydro steroids by subjecting a steroid saturated in the 1:2- and/or 4:5-position to the aerobic action of an enzyme of Didymella lycopersici, Calonectria decora, Alternaria passiflorae, Ophiobolus heterostrophus or Ophiobolus miyabeanus. Starting steroids may be derivatives of spirostane, furostane, cholane, pregnane, testane and their allo isomers, and may be saturated or unsaturated and contain in addition to a 3-free or functionally converted hydroxyl or oxo group other substituents, e.g. oxo, hydroxyl, carboxyl, epoxy or halo, in positions 6, 7, 8, 9, 11, 12, 14, 15, 16, 17, 18, 20 and 21; many compounds are specified. In examples: (1) cortexone in acetone is incubated with Calonectria decora for 2 days at 27 DEG  C., the mixture extracted with ethyl acetate, chromatographed on silica gel and eluted with chloroform-acetone giving 1-dehydrocortexone; (2) as in (1) using Alternaria passiflorae, Ophiobolus heterostrophus, or O. miyabeanus as the organism; (3) to (5), (10), (12) to (16), as in (1) there are prepared 1-dehydrocortisone, characterized as its 21-acetate, oenanthate, and undecylenate, 1-dehydrohydrocortisone, 1-dehydroaldosterone, D 1,4 - androstadiene - 3,17 - dione, D 1,4 - 3,11,20 - triketo - 21 - hydroxypregnadiene (also its acetate, oenanthate and undecylenate), 1-dehydrocorticosterone and its 21-acetate, 1-dehydro-17a -hydroxycortexone and its 21-acetate, and 1-dehydroprogesterone; (6) and (7), the following compounds incubated with each of the above organisms gave the corresponding D 1,4-derivatives: cortexone, cortisone, hydrocortisone, 17a -hydroxycortexone, corticosterone, 11 - epicorticosterone, 11 - epihydrocortisone, aldosterone, 17a  - hydroxyaldosterone, progesterone, pregnenolone, 21 - hydroxypregnenolone, D 5 - androsten - 3b  - ol - 17 - one and D 4 - androstene - 3,17 - dione; (8) and (9) 3,11,20 - triketo - 17a ,21 - dihydroxy allopregnane and its 11b -hydroxy analogue with C. decora give 1-dehydrocortisone and 1-dehydrohydrocortisone; (11) 1-dehydrocortexone is converted to its 21-acetate; (17) to (28) the following steroids are incubated with Didymella lycopersici giving the corresponding D 1,4-steroids: cortexone, cortisone, hydrocortisone, 3,11,20 - triketo - 17a ,21 - dihydroxyallopregnane, progesterone, D 1-allopregnene-3,20-dione, pregnane - 3,20 - dione, corticosterone, 11 - dehydrocorticosterone, 17a  - hydroxycortexone, testosterone, D 1- and D 4-androstene-3,17-dione, D 4 - 3,11,20 - trioxo - 17a  - methyl - 21 - acetoxypregnene, 17a  - ethinyltestosterone, 6 - dehydro-cortexone - 21 - acetate, 11 - dehydroprogesterone, 17a  - methyltestosterone, 9a  - fluorohydrocortisone, and 9,11b  - oxido - 17a -hydroxycortexone - 21 - acetate; (28) cleavage of 1 - dehydro - 9,11b  - oxido - 17a  - hydroxycortexone 21-acetate with HF gives 1-dehydro-9a  - fluorohydrocortisone 21 - acetate.  Specification 792,803 is referred to.